19-15087456-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001004713.2(OR1I1):​c.391C>T​(p.Arg131Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000582 in 1,613,992 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

OR1I1
NM_001004713.2 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.328
Variant links:
Genes affected
OR1I1 (HGNC:8207): (olfactory receptor family 1 subfamily I member 1) Olfactory receptors interact with odorant molecules in the nose, to initiate a neuronal response that triggers the perception of a smell. The olfactory receptor proteins are members of a large family of G-protein-coupled receptors (GPCR) arising from single coding-exon genes. Olfactory receptors share a 7-transmembrane domain structure with many neurotransmitter and hormone receptors and are responsible for the recognition and G protein-mediated transduction of odorant signals. The olfactory receptor gene family is the largest in the genome. The nomenclature assigned to the olfactory receptor genes and proteins for this organism is independent of other organisms. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.20418066).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
OR1I1NM_001004713.2 linkuse as main transcriptc.391C>T p.Arg131Cys missense_variant 2/2 ENST00000641398.1 NP_001004713.1 O60431

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
OR1I1ENST00000641398.1 linkuse as main transcriptc.391C>T p.Arg131Cys missense_variant 2/2 NM_001004713.2 ENSP00000493393.1 O60431
OR1I1ENST00000209540.2 linkuse as main transcriptc.391C>T p.Arg131Cys missense_variant 1/16 ENSP00000209540.2 O60431

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152182
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000318
AC:
8
AN:
251206
Hom.:
0
AF XY:
0.0000221
AC XY:
3
AN XY:
135792
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000704
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000595
AC:
87
AN:
1461810
Hom.:
0
Cov.:
60
AF XY:
0.0000564
AC XY:
41
AN XY:
727214
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000737
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000460
AC:
7
AN:
152182
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74352
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000387
Hom.:
0
Bravo
AF:
0.0000604
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000233
AC:
2
ExAC
AF:
0.0000494
AC:
6
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJan 18, 2022The c.391C>T (p.R131C) alteration is located in exon 1 (coding exon 1) of the OR1I1 gene. This alteration results from a C to T substitution at nucleotide position 391, causing the arginine (R) at amino acid position 131 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.076
BayesDel_addAF
Benign
-0.39
T
BayesDel_noAF
Benign
-0.62
CADD
Benign
15
DANN
Uncertain
1.0
DEOGEN2
Benign
0.018
T;T
Eigen
Benign
-0.24
Eigen_PC
Benign
-0.43
FATHMM_MKL
Benign
0.020
N
LIST_S2
Uncertain
0.88
.;D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.20
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.1
M;M
PrimateAI
Benign
0.17
T
PROVEAN
Uncertain
-3.3
.;D
REVEL
Benign
0.042
Sift
Uncertain
0.0070
.;D
Sift4G
Uncertain
0.0040
.;D
Polyphen
0.99
D;D
Vest4
0.15
MVP
0.42
MPC
0.28
ClinPred
0.67
D
GERP RS
2.7
Varity_R
0.18
gMVP
0.15

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs372952340; hg19: chr19-15198267; COSMIC: COSV52918032; API